Search

Endoplasmic reticulum (ER) stress and mitochondrial dysfunction play a pivotal role in the pathological process of sepsis-induced acute lung injury (ALI). Quercetin has been proved to exert anti-inflammation in ALI. This study aimed to explore the protection mechanism of quercetin against sepsis-induced ALI via suppressing ER stress and mitochondrial dysfunction. Cecal ligation and puncture (CLP) mouse model was established to mimic sepsis, and LPS was used to stimulate murine lung epithelial (MLE-12) cells. We observed that quercetin ameliorated pulmonary pathological lesion and oxidative damage in sepsis-induced mice. In LPS-stimulated MLE-12 cells, quercetin could inhibit the level of ER stress as evidenced by decreased mRNA expression of PDI, CHOP, GRP78, ATF6, PERK, IRE1α and improve mitochondrial function, as presented by increased MMP, SOD level and reduced production of ROS, MDA. Meanwhile, transcriptome analysis revealed that quercetin upregulated SIRT1/AMPK mRNA expression. Furthermore, we used siRNA to knockdown SIRT1 in MLE-12 cells, and we found that SIRT1 knockdown could abrogate the quercetin-elicited antioxidation in vitro. Therefore, quercetin could protect against sepsis-induced ALI by suppressing oxidative stress-mediated ER stress and mitochondrial dysfunction via induction of the SIRT1/AMPK pathways. • The present study linked the anti-inflammatory and antioxidant of quercetin to endoplasmic reticulum (ER) stress and mitochondrial dysfunction. • In this study, we focused on the protective effects of quercetin on sepsis-induced ER stress and mitochondrial dysfunction via activating the SIRT1/AMPK pathway and its potential therapeutic effects on sepsis-induced ALI. I feel that we provided the evidence that sepsis destroys alveolar epithelial cells by causing ER stress and mitochondrial dysfunction leading to acute lung injury. Notably, quercetin mitigated ER stress and mitochondrial dysfunction through the SIRT1/AMPK pathways both in vivo and in vitro. • To further explore the underlying mechanism of quercetin on ALI, we performed a transcriptome study by RNA-seq. Transcriptome analysis revealed that quercetin markedly elevated the mRNA level of SIRT1 and AMPK. [ABSTRACT FROM AUTHOR]